bHistorically it has been accepted, and recent research has established, that silver (Ag) is an efficacious antimicrobial agent. A dwindling pipeline of new antibiotics, combined with an increase in the number of antibiotic-resistant infections, is bringing Ag to the fore as a therapeutic compound to treat infectious diseases. Currently, many formulations of Ag are being deployed for commercial and medical purposes, with various degrees of effectiveness at killing microbial cells. H istory has demonstrated that silver (Ag) is an efficacious antimicrobial agent, finding utility as an antiquated preservative for food and water (1, 2). Currently, Ͼ100 Ag-containing medical devices have been approved for use by the FDA (http: //www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn .cfm), and there is mounting evidence that Ag may be effective for preventing the spread of infectious disease (1,3,4). Although the toxicological profile of orally administered Ag remains to be resolved, topical application for the treatment of chronic wounds remains promising (5-8). Accordingly, Ag can address a timely public health issue, as chronic wounds represent a substantial financial and medical burden to the health care system. One of the hallmarks of a chronic wound is the presence of a biofilm, a factor that complicates wound healing and is hypothesized to be the fulcrum between the acute-to-chronic-wound transition (6, 9-15). Also, bacterial biofilms contaminate implanted medical devices (16) and exhibit high-level resistance to conventional antibiotics (17-23). New antibiofilm agents are thus desperately needed in medicine.Recently, researchers have demonstrated that Ag formulations also have potential as antibiofilm agents; these formulations include silver sulfadiazine (AgSD) (24), Ag nanoparticles (AgNPs) (25, 26), and silver nitrate (AgNO 3 ) (27). Currently, the wound care industry is replete with Ag-based ointments and wound dressings with claimed efficacy at reducing bacterial bioburden (7,(28)(29)(30)(31)(32). However, only a few antibiofilm products exist. There are numerous reasons why this is so: (i) current standardized, antimicrobial testing methods focus on bacteria in their planktonic state and not as biofilms (33, 34); (ii) biofilms are characteristically more tolerant to metal poisoning (35-38); and (iii) the detailed mechanism of action for the toxicity of Ag to biofilms remains to be fully described (1).The antimicrobial activity of Ag is intrinsically dependent on the formation of the Ag 1ϩ ion (7, 39). Briefly, Ag 1ϩ , a Lewis soft acid, poisons the microbial cell by binding to reduced thiols (SH), impairing membrane function (1), and disrupting ironsulfur clusters (40). That being said, the antimicrobial efficacy of higher oxidation states of Ag, Ag 2ϩ and Ag 3ϩ , has not been given adequate consideration, mainly due to instability in solution. A promising resolution to the instability of higher oxidation states of Ag is silver oxysalts, for example, Ag(Ag 3 O 4 ) 2 X, the most stable of which is coordina...